Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence showed more and more importance of the epigenetic contribution, especially the DNA methylation, to the pathogenesis of rheumatoid arthritis. Identification of aberrant DNA methylation regions in RA would provide important for the comprehensively understand to the pathogenesis of rheumatoid.
Methods: We performed a genome-wide DNA methylation study in CD4+ T cells in 12 rheumatoid arthritis patients compared to 12 matched normal healthy controls. CD4+ T cells were prepared from freshly isolated PBMCs by depleting cells expressing CD8, CD14, CD16, CD19, CD36, CD56, CD123, γ/δ T cell receptors, and glycophorin A using No-Touch T cell isolation kits (Miltenyi Biotec). The purity of the CD4+ T cells was 95–98%, as determined by flow cytometry using specific antibodies.Cytosine methylation status was quantified with Illumina methylation 450K microarray (HM450K, 485512 CpG sites). Beta-mixture quantile normalization, batch effect correction, outlier probe imputation were applied in the data pre-processing to keep the data creditable for the follow analysis.
Results: We identified 810 hypomethylated and 392 hypermethylated CG sites in RA CD4+ T cells compared to normal controls, representing 383 and 785 genes hypermethylated and hypomethylated in RA patients (P<3.4×10-7). Cluster analysis based on significantly differential methylated loci showed distinct separation between RA and normal controls. Gene ontology analysis showed alternative splicing (P=1.2×10-7, FDR) and phosphoprotein (1.7×10-2, FDR) were significantly aberrant in RA patients, indicating the abnormal of transcript alternative splicing and protein modification mediated by DNA methylation might play important role in the pathogenesis of rheumatoid arthritis. What’s more, the result showed human leukocyte antigen (HLA) region was frequently hypomethylated in RA patients, including HLA-DRB6, HLA-DQA1 and HLA-E, however, HLA-DQB1 showed different methylation profiles with significant hypermethylation in CpG island region and hypomethylation in CpG shelf region. Outsite of the MHC region, the most hypermethylated genes in RA included HDAC4, NXN, TBCD and TMEM61 while the most significant hypomethylated genes included ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9.
Conclusion: Genome-wide DNA methylation patterns revealed significant DNA methylation change in CD4+ T cells from patients with rheumatoid arthritis which might provide contribution to the pathogenesis of rheumatoid arthritis
To cite this abstract in AMA style:Guo S, Jiang T, Wang R, Shen Y, Zhu X, Bai F, Ding Q, Chen G, He D. Genome-Wide DNA Methylation Patterns in CD4+ T Reveal Significant Contribution of DNA Methylation to Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/genome-wide-dna-methylation-patterns-in-cd4-t-reveal-significant-contribution-of-dna-methylation-to-rheumatoid-arthritis/. Accessed January 22, 2022.
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